Diurnal variation of islet autoantibody titers in established type 1 diabetes suggests restricted-time sampling improves aab measurement and detection

Abstract Diurnal islet autoantibody (Aab) variation in type 1 diabetes (T1D) remains poorly understood and could hinder efforts to develop, test and refine new therapies. We sought to describe the extent and pattern of diurnal variation in islet autoantibodies and, having found significant variation, translate to the clinical setting. We conducted two studies in human subjects with established T1D: (1) a prospective study (n = 10) of the range of islet autoantibody and immunoglobulin daily variation within humans and (2) an independent retrospective, cross-sectional study (n = 705) of the effect of time of sample collection on Aab titer and detection in clinical settings. We found that some individuals have wide Aab variations during the day and which can exceed expected levels of inter-assay variation. For some Aab, this variation followed a circadian pattern. We also found that, in clinical settings, time-restricted sampling can lead to increased IA-2A and ZnT8A detection within specific age-groups. We conclude that time-restriction can potentially improve the use of Radiobinding-measured Aabs as biomarkers for the development and monitoring of disease-modifying therapies and in developing islet transplantation strategies in established T1D. Investigation of diurnal Aab variation and time restriction is needed in early-stage disease.